The 1500–1700 nm spectral range in short wave infrared (SWIR) region allows for biological imaging with large imaging depth, high contrast and resolution. However, very few SWIR imaging probes exist, and rarely reported probes (e.g., rare‐earth‐based ones with excitation at 980 nm) are often associated with biological heating effect. Here, a class of erbium (Er3+)‐sensitized core–shell nanocrystals of NaErF4:Yb3+@NaLuF4, which emit efficient SWIR luminescence peaked at 1525 nm under 808 nm excitation, without producing any local heating, is described. The inert shell inhibits concentration‐dependent quenching and allows for an enriched incorporation of 100% Er3+ into the core, yielding about ≈650‐fold higher SWIR luminescence than parent core nanocrystals. Importantly, an appropriate doping of ytterbium (Yb3+) (optimized concentration, 20%) into the core is shown to further enhance SWIR luminescence (by twofold), endowing the nanocrystals with a high quantum yield of 11%. This Yb3+‐mediated enhancement is possibly due to the suppression of upconverting pathways and the formation of energy trapping centers that prevent the energy migration to intrinsic lattice defects. These bright SWIR core/shell nanocrystals allow high contrast in vitro imaging of HeLa cells and in vivo through‐skull imaging of blood vasculature in the mouse brain.
Fluorescence (FL) and X-ray computed tomography (CT) imaging-guided photodynamic therapy (PDT) can provide a powerful theranostic tool to visualize, monitor, and treat cancer and other diseases with enhanced accuracy and efficacy.
Methods:
In this study, clinically approved iodinated CT imaging contrast agent (CTIA) iodixanol and commercially available photosensitizer (PS) meso-tetrakis (4-sulphonatophenyl) porphine (TPPS
4
) were co-encapsulated in biocompatible PEGylated nanoliposomes (NL) for enhanced anticancer PDT guided by bimodal (FL and CT) imaging.
Results:
The NL co-encapsulation of iodixanol and TPPS
4
(LIT) lead to an increase in singlet oxygen generation by PS via the intraparticle heavy-atom (iodine) effect on PS molecules, as it was confirmed by both direct and indirect measurements of singlet oxygen production. The confocal imaging and PDT of cancer cells were performed
in vitro
, exhibiting the cellular uptake of TPPS
4
formulations and enhanced PDT efficacy of LIT. Meanwhile, bimodal (FL and CT) imaging was also conducted with tumor-bearing mice and the imaging results manifested high-efficient accumulation and retention of LIT in tumors. Moreover, PDT of tumor
in vivo
was shown to be drastically more efficient with LIT than with other formulations of TPPS
4
.
Conclusion:
This study demonstrated that LIT can serve as a highly efficient theranostic nanoplatform for enhanced anticancer PDT guided by bimodal (FL and CT) imaging.
In this work, the application of near infrared (NIR)‐emitting NaYbF4:1%Tm3+@NaLuF4:30%Nd3+ core–shell nanoparticles is reported for noninvasive probing and monitoring the temperature during photopolymerization of dental materials. When excited at 808 nm, the synthesized nanoparticles emit NIR photoluminescence (PL) with two distinctive peaks at 865 and 980 nm which correspond to radiative transitions from the doped Nd3+ and Yb3+ ions, respectively. Luminescence intensity ratio between these two bands is found to vary with temperature due to temperature‐dependent electronic excitation energy transfer between Nd3+ and Yb3+ ions at the core/shell interface. This finding allows luminescence ratiometric evaluation of the in situ temperature during photopolymerization of resin cement (doped with nanoparticles) in a veneer placement procedure. In addition, the NIR emission also enables PL imaging of the distribution of the adhesive under the veneer. The results highlight that rare‐earth ions–doped nanoparticles with both excitation and emission in the NIR spectral range are advantageous for both PL‐based nanothermometry and imaging due to the reduced attenuation of NIR light by dental ceramics.
Optical bioimaging with exogenous luminophores emitting in short-wave infrared spectral region (SWIR, ~ 1000–1700 nm) is a rapidly developing field, and the development of multiple SWIR-photoluminescent nanoprobes has recently been reported. In this regard, hyperspectral imaging (HSI), combined with unmixing algorithms, is a promising tool that can allow for efficient multiplexing of the SWIR-emitting nanoagents by their photoluminescence (PL) spectral profiles. The SWIR HSI technique reported here is developed to multiplex two types of nanoprobes: polymeric nanoparticles doped with organic dye (PNPs) and rare-earth doped fluoride nanoparticles (RENPs). Both types of nanoprobes exhibit PL in the same spectral range (~ 900–1200 nm), which hinders spectral separation of PL with optical filters and limits possibilities for their multiplexed imaging in biological tissues. By applying SWIR HSI, we exploited differences in the PL spectral profiles and achieved the spectrally selective and sensitive imaging of the PL signal from every type of nanoparticles. Unmixing of acquired data allowed for multiplexing of the spectrally overlapping nanoprobes by their PL profile. Both quantitative and spatial distribution for every type of nanoparticles were obtained from their mixed suspensions. Finally, the SWIR HSI technique with unmixing protocol was applied to in vivo imaging of mice subcutaneously injected with PNPs and RENPs. The applicability of hyperspectral techniques to multiplex nanoprobes in the in vivo imaging was successfully demonstrated.
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